Particulate agents

- Syngenix Limited

A novel means of pharmaceutical delivery for therapy of prophylaxis or to assist surgical or diagnostic operations on the living body is provided by neuronal endocytosis and axonal transport following pharmaceutical administration into vascularized, peripherally innervated tissue, e.g. intramuscular injections of a nerve adhesion molecule in coupled particle comprising a physiologically active substance or a diagnostic marker.

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Claims

1. A method of treating a living human or non-human body to generate a therapeutic or prophylactic treatment or assist diagnostic investigation or surgical treatment thereof, said method comprising administering into a vascularized peripherally innervated tissue site or into other tissue sites innervated by a spinal root a particulate pharmaceutical agent comprising a nerve adhesion moiety serving to promote neuronal endocytosis of said agent and a physiologically active or diagnostic marker moiety for axonal transport from said tissue site.

2. A method of treating a living human or non-human body in need of therapeutic, prophylactic or diagnostic treatment, comprising administering into a vascularized peripherally innervated tissue site or into other tissue sites innervated by a spinal root, a therapeutic, prophylactic or diagnostic composition comprising a nerve adhesion moiety wherein said nerve adhesion moiety is a particulate pharmaceutical agent subject to neuronal endocytosis, said agent further comprising a physiologically active or diagnostic marker moiety for axonal transport following neuronal endocytosis of said agent.

3. A pharmaceutical agent comprising a nerve adhesion molecule coupled to an optionally-coated, particulate, physiologically active or diagnostically marked substance, said substance being one selected from the group consisting of metal oxide, metal sulfide and alloy when said substance is diagnostically marked, wherein said physiologically active or diagnostically marked substance is axonal transport following neuronal endocytosis of said agent, and wherein said particulate have a mean particle size of 10-50 nm.

4. A composition as claimed in claim 4 wherein said particles have a spinel structure.

5. A composition as claimed in claim 5 wherein said particles are superparamagnetic.

6. A composition as claimed in claim 6 wherein said particles incorporate radionuclides.

7. The method, according to claim 1, wherein said particulate pharmaceutical agent is administered in solution.

8. The method, according to claim 1, wherein said particulate pharmaceutical agent comprises a carrier particle coated with a hydrophilic molecule to which said nerve adhesion moiety and said physiologically active or diagnostically marked moiety are bound.

9. The method, according to claim 8, wherein said hydrophilic molecule is dextran.

10. The method, according to claim 8, wherein said carrier particle is a metal oxide.

11. The method, according to claim 2, wherein said particulate pharmaceutical agent is administered in solution.

12. The method, according to claim 2, wherein said particulate pharmaceutical agent comprises a carrier particle coated with a hydrophilic molecule to which said nerve adhesion moiety and said physiologically active or diagnostically marked moiety are bound.

13. The method, according to claim 12, wherein said hydrophilic molecule is dextran.

14. The method, according to claim 12, wherein said carrier particle is a metal oxide.

15. The pharmaceutical agent, according to claim 3, wherein said pharmaceutical agent is administered in solution.

16. The pharmaceutical agent, according to claim 4, wherein said pharmaceutical agent comprises a carrier particle coated with a hydrophilic molecule to which said nerve adhesion moiety and said physiologically active or diagnostically marked moiety are bound.

17. The pharmaceutical agent, according to claim 16, wherein said hydrophilic molecule is dextran.

18. The method, according to claim 16, wherein said carrier particle is a metal oxide.

19. A pharmaceutical agent comprising a nerve-adhesion molecule coupled to an optionally-coated, particulate, physiologically active or diagnostically marked substance, said substance being one selected from the group consisting or metal oxide, metal sulphide and alloy when said substance is diagnostically marked, wherein said physiologically active or diagnostically marked substance is for axonal transport following neuronal endocytosis of said agent.

Referenced Cited
U.S. Patent Documents
4430320 February 7, 1984 Shigematsu et al.
4452773 June 5, 1984 Molday
4479940 October 30, 1984 Bizzini
4552145 November 12, 1985 Riley et al.
4594336 June 10, 1986 Bizzini
4690130 September 1, 1987 Mirell
4752567 June 21, 1988 De Brabander et al.
4813399 March 21, 1989 Gordon
4827945 May 9, 1989 Groman et al.
4849210 July 18, 1989 Widder
4863715 September 5, 1989 Jacobsen et al.
5019369 May 28, 1991 Presant et al.
5043101 August 27, 1991 Gordon
5077035 December 31, 1991 Wieland et al.
5169933 December 8, 1992 Anderson et al.
5248772 September 28, 1993 Siiman et al.
5382468 January 17, 1995 Chagnon et al.
5424288 June 13, 1995 Order
5492814 February 20, 1996 Weissleder
5554498 September 10, 1996 Filler et al.
Foreign Patent Documents
0455093 November 1991 EPX
8601112 February 1986 WOX
8800060 January 1988 WOX
8909625 October 1989 WOX
9001295 February 1990 WOX
9101144 February 1991 WOX
9104014 April 1991 WOX
Other references
  • Gallagher, J.E., G. George, A.R. Brody (1987) "Sialic acid mediates the initial binding of positively charged inorganic particles to alveolar macrophage membranes" Am. Rev. Respir. Dis. 135(6):1345-1352 (abstract only). Menetrey, D. (1985) "Retrograde tracing of neural pathways with a protein-gold complex" Histochemistry 83(5):391-395 (abstract only).
Patent History
Patent number: 5948384
Type: Grant
Filed: Jun 7, 1995
Date of Patent: Sep 7, 1999
Assignee: Syngenix Limited
Inventor: Aaron Gershon Filler (Seattle, WA)
Primary Examiner: Jose G. Dees
Assistant Examiner: Dameron Jones
Law Firm: Saliwanchik, Lloyd & Saliwanchik
Application Number: 8/473,697
Classifications
Current U.S. Class: 424/129; 424/111; 424/137
International Classification: A61K 5100; A61M 3614;